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Long-term study of the clinical significance of loss of heterozygosity in childhood acute lymphoblastic leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is one of the most common malignancies in childhood, with a widely variable outcome. Differences in the behavior and prognosis of the leukemia suggest that ALL can be divided into several biologic subgroups. We analyzed the loss of heterozygosity (LOH) of 6q, 9p, 11q and 12p using 31 microsatellite sites to determine their overall frequency and clinical value. We have studied 244 primary ALL samples obtained from the Multicenter Trial ALL-BFM 90 of Childhood ALL group. These patients have now been followed clinically for over 8 years. LOH occurred in 169 (69%) individuals in the following frequencies: 6q, 49 patients (20%); 9p, 97 patients (40%); 11q, 29 patients (12%); 12p, 60 patients (25%). Clinical data showed that those with 6q LOH were younger (P = 0.01) and had lower WBC counts (P = 0.02); patients with 9p LOH more frequently had CNS involvement (P = 0.01) and T cell phenotype (P = 0.0001); individuals with 11q LOH had a good response to induction chemotherapy (P = 0.02); those with 12p LOH were younger (P = 0.005), frequently had precursor B ALL (P = 0.001), and had a longer event-free survival (P = 0.05). Taken together, these data confirm that LOH is a very frequent alteration in childhood ALL.

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Acknowledgements

This study was supported in part by National Institutes of Health, Lymphoma Foundation, C and H Koeffler Fund, Parker Hughes Trust, Horn Fund (HPK), the Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe (CRB), and Grant-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan (ST). HPK is a member of the Jonsson Comprehensive Cancer Center and holds the endowed Mark Goodson Chair of Oncology Research at Cedars-Sinai Medical Center/UCLA School of Medicine. We are grateful to Wolf Dieter Ludwig for providing the immunophenotypic data. We thank Ian K Williamson, Harry E Taub and Jeffrey Grewal for technical help.

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Takeuchi, S., Tsukasaki, K., Bartram, C. et al. Long-term study of the clinical significance of loss of heterozygosity in childhood acute lymphoblastic leukemia. Leukemia 17, 149–154 (2003). https://doi.org/10.1038/sj.leu.2402727

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